Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials

Godela M. Brosnahan, Kaleab Z. Abebe, Charity G. Moore, Frederic F. Rahbari-Oskoui, Kyongtae T. Bae, Jared J. Grantham, Robert W. Schrier, William E. Braun, Arlene B. Chapman, Michael F. Flessner, Peter C Harris, Marie C Hogan, Ronald D. Perrone, Dana C. Miskulin, Theodore I. Steinman, Vicente Torres

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Abstract

Background: Previous clinical studies of autosomal dominant polycystic kidney disease (ADPKD) reported that loss of kidney function usually follows a steep and relentless course. A detailed examination of individual patterns of decline in estimated glomerular filtration rate (eGFR) has not been performed. Study Design: Longitudinal post hoc analysis of data collected during the Halt Progression of Polycystic Kidney Disease (HALT-PKD) trials. Setting & Participants: 494 HALT-PKD Study A participants (younger; preserved eGFR) and 435 Study B participants (older; reduced eGFR) who had more than 3 years of follow-up and 7 or more eGFR assessments. Measurements: Longitudinal eGFR assessments using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation. Predictors: Demographic, clinical, laboratory, and imaging features of participants. Outcomes: Probability of linear and nonlinear decline patterns or of stable eGFR calculated for each participant from a Bayesian model of individual eGFR trajectories. Results: Most (62.5% in Study A and 81% in Study B) participants had a linear decline in eGFR during up to 8 years of follow-up. A proportion (22% in Study A and 13% in Study B) of progressors had a nonlinear pattern. 15.5% of participants in Study A and 6% in Study B had a prolonged (≥4.5 years) period of stable eGFRs. These individuals (Study A) had significantly smaller total kidney volumes, higher renal blood flows, lower urinary albumin excretion, and lower body mass index at baseline and study end. In Study B, participants with reduced but stable eGFRs were older than the progressors. Two-thirds of nonprogressors in both studies had PKD1 mutations, with enrichment for weak nontruncating mutations. Limitations: Relatively short follow-up of a clinical trial population. Conclusions: Although many individuals with ADPKD have a linear decline in eGFR, prolonged intervals of stable GFRs occur in a substantial fraction. Lower body mass index was associated with more stable kidney function in early ADPKD.

Original languageEnglish (US)
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Jan 1 2018

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Keywords

  • Autosomal dominant polycystic kidney disease (ADPKD)
  • Bayesian models
  • EGFR slope
  • EGFR trajectory
  • End-stage renal disease (ESRD)
  • Estimated glomerular filtration rate (eGFR)
  • Kidney disease progression
  • Mutation analysis
  • Total kidney volume

ASJC Scopus subject areas

  • Nephrology

Cite this

Brosnahan, G. M., Abebe, K. Z., Moore, C. G., Rahbari-Oskoui, F. F., Bae, K. T., Grantham, J. J., Schrier, R. W., Braun, W. E., Chapman, A. B., Flessner, M. F., Harris, P. C., Hogan, M. C., Perrone, R. D., Miskulin, D. C., Steinman, T. I., & Torres, V. (Accepted/In press). Patterns of Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis From the HALT-PKD Trials. American Journal of Kidney Diseases. https://doi.org/10.1053/j.ajkd.2017.10.023